模擬DNA於脂雙層上自發展開之行為

Simulating the Spontaneous Unraveling of DNA on Lipid Bilayers

王靜寬(Ching-Kuan Wang)

指導教授 ： 謝之真

國立臺灣大學/工學院/化學工程學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201603147

摘要

DNA於鋪有正電脂雙層的玻璃溝槽與其側壁夾角處拉伸的現象，是因為該處具有一帶狀位能井的結果。但本實驗室所測得之DNA拉伸率與位能井寬度的關係與理論預測有所偏差，我們認為與位能井的形狀有關，故運用模擬方法來進行檢驗。
我們運用布朗動態法（Brownian dynamics, BD）模擬DNA在2D侷限環境下的性質，布朗動態法透過對高分子鏈施予隨機力模擬DNA於脂雙層上運動，而侷限環境則來自於我們所設定的一帶狀位能井。我們使用bead-spring model來模擬DNA，模型中包含Lennard-Jones體積排斥力、彈簧力及撓曲力之作用，在無限深方形位能井的條件下，我們的模擬結果與Odijk及de Gennes的預測情形相同。
首先我們模擬DNA在固定侷限寬度的情況下改變位能井侷限深度的拉伸情形，發現當位能井深度變大，DNA拉伸率也隨之上升，當位能井深度小於系統熱擾動能量時，DNA的運動會開始超出侷限範圍，導致其拉伸率快速下降，到最後完全離開侷限區域，此現象與我們在實驗上的觀察相同。
接著我們模擬位能井深度隨侷限寬度增加而變淺的情形，此趨勢是源自於我們實驗所觀察到的現象。我們的模擬結果顯示位能井的深度與侷限寬度對DNA拉伸率有高度影響，若運用與實驗近似的深度下降趨勢去進行模擬，所得之結果與理論趨勢的對應情形會與實驗所得高度近似。故我們的模擬結果證實了我們對位能井提出的假設，同時也佐證了DNA在帶狀侷限下，實驗結果與理論預期上的偏差。

關鍵字

DNA ； 帶狀侷限 ； 脂雙層 ； 布朗動態法

並列摘要

When DNA adsorbed on grooved glass with cationic lipid bilayers, they extend along the roots of the side wall of the grooves where the surface curvature is positive. The phenomenon is spontaneous and is expected to be caused by a deep energy well there. Such energy well can be considered as a strip-like confinement for DNA, and the width of the strip can be inferred from the width of area with positive curvature. However, the experimentally determined relationship between DNA extension and strip width somewhat deviates from the theoretical predictions made by de Gennes and Odijk. We suspect this deviation is related to the shape of the energy well which is assumed to be a deep square but is more likely to be nearly parabolic in reality.
To support our argument, we use Brownian dynamics to simulate DNA behavior in a strip confinement. DNA is represented by a bead-spring model that includes Lennard-Jones excluded-volume force, spring force and bending force. The force applied by lipid molecules is simulated by a random force. The model was tested in a strip confinement with infinitely deep well and the results were founded to match predictions by de Gennes and Odijk.
At first we simulate DNA extension in a fixed depth of energy well with varying confinement width. DNA extension was found decreases with increasing width of energy well. As we expected, the simulation results are not in agreement with theoretical prediction. As the second step, we simulate DNA extension under a fixed width of confinement with varying depth of energy well. We found that DNA extension gradually increases as the energy well gets deeper. If the depth of energy well is below the thermal energy of the system, DNA starts to cross the boundary of confinement and the degree of DNA extension drops rapidly. With further reducing the depth of the energy well, DNA can no longer be confined by the well.
We also simulate the cases that the depth of energy well decrease while the width of confinement increase because such scenario is closer to the real situation in experiments. We find that the relative rate of change between the depth of energy well and the width of confinement has critical influence to DNA extension. Employing a relationship between the depth of energy well and the width of confinement similar to experimental condition, we found the simulation results show very similar deviation from theoretical prediction as the experiments do. In conclusion, the simulation results support our argument that the energy well is not a deep square in reality. This finding also bridges the gap between the theoretical predictions and experimental observation for DNA behavior in strip confinement.

並列關鍵字

DNA ； strip confinement ； lipid bilayers ； Brownian dynamics

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